Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNAs (mRNAs). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent...
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| Format: | Article |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:236595 |
| Online Access: | https://ddd.uab.cat/record/236595 https://dx.doi.org/urn:doi:10.1073/pnas.2003358117 |
| Access Level: | Open access |
| Keyword: | Cancer Epigenetics Transfer RNA |
| _version_ | 1878736541930487808 |
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| author | Rosselló-Tortella, Margalida|||0000-0003-4610-7981 |
| author2 | Llinàs-Arias, Pere|||0000-0002-3666-0532 Sakaguchi, Y. Miyauchi, K. Davalos, Veronica|||0000-0003-4077-5137 Setien, Fernando|||0000-0002-4061-4635 Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Piñeyro, David|||0000-0001-5633-3339 Martínez-Gómez, Jesús|||0000-0002-7770-073X Guil, Sonia|||0000-0002-2257-3331 Joshi, Ricky S.|||0000-0003-4463-0453 Villanueva, Alejandro|||0000-0001-5164-0006 Suzuki, Tsutomu Esteller, M.|||0000-0003-4490-6093 |
| author2_role | author author author author author author author author author author author author author |
| author_browse | Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Davalos, Veronica|||0000-0003-4077-5137 Esteller, M.|||0000-0003-4490-6093 Guil, Sonia|||0000-0002-2257-3331 Joshi, Ricky S.|||0000-0003-4463-0453 Llinàs-Arias, Pere|||0000-0002-3666-0532 Martínez-Gómez, Jesús|||0000-0002-7770-073X Miyauchi, K. Piñeyro, David|||0000-0001-5633-3339 Rosselló-Tortella, Margalida|||0000-0003-4610-7981 Sakaguchi, Y. Setien, Fernando|||0000-0002-4061-4635 Suzuki, Tsutomu Villanueva, Alejandro|||0000-0001-5164-0006 |
| author_facet | Rosselló-Tortella, Margalida|||0000-0003-4610-7981 Llinàs-Arias, Pere|||0000-0002-3666-0532 Sakaguchi, Y. Miyauchi, K. Davalos, Veronica|||0000-0003-4077-5137 Setien, Fernando|||0000-0002-4061-4635 Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Piñeyro, David|||0000-0001-5633-3339 Martínez-Gómez, Jesús|||0000-0002-7770-073X Guil, Sonia|||0000-0002-2257-3331 Joshi, Ricky S.|||0000-0003-4463-0453 Villanueva, Alejandro|||0000-0001-5164-0006 Suzuki, Tsutomu Esteller, M.|||0000-0003-4490-6093 |
| author_role | author |
| collection | Dipòsit Digital de Documents de la UAB |
| description | Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNAs (mRNAs). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_90de7cee5048c4e4cdeeed1a2dfd9d68 |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ddd.uab.cat:236595 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer Rosselló-Tortella, Margalida|||0000-0003-4610-7981 Llinàs-Arias, Pere|||0000-0002-3666-0532 Sakaguchi, Y. Miyauchi, K. Davalos, Veronica|||0000-0003-4077-5137 Setien, Fernando|||0000-0002-4061-4635 Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Piñeyro, David|||0000-0001-5633-3339 Martínez-Gómez, Jesús|||0000-0002-7770-073X Guil, Sonia|||0000-0002-2257-3331 Joshi, Ricky S.|||0000-0003-4463-0453 Villanueva, Alejandro|||0000-0001-5164-0006 Suzuki, Tsutomu Esteller, M.|||0000-0003-4490-6093 Cancer Epigenetics Transfer RNA Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNAs (mRNAs). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology. https://ddd.uab.cat/record/236595 https://dx.doi.org/urn:doi:10.1073/pnas.2003358117 |
| spellingShingle | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer Rosselló-Tortella, Margalida|||0000-0003-4610-7981 Cancer Epigenetics Transfer RNA |
| title | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| title_full | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| title_fullStr | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| title_full_unstemmed | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| title_short | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| title_sort | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
| topic | Cancer Epigenetics Transfer RNA |
| topic_facet | Cancer Epigenetics Transfer RNA |
| url | https://ddd.uab.cat/record/236595 https://dx.doi.org/urn:doi:10.1073/pnas.2003358117 |